DPEP1 and TPX2 as independent predictors of cancer-specific mortality in pancreatic ductal adenocarcinoma

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	CANCER-29

* FARE Award Winner

Authors

• G Zhang
• A Schetter
• P He
• N Funamizu
• P Hussain

Abstract

In the current study, we aimed to identify biologically relevant genes with prognostic and therapeutic significance in PDAC. Fifty-three genes that were differentially expressed and associated with survival in microarray studies were evaluated using quantitative RT-PCR in the test cohort (N=45) and further validated in an independent validation cohort (N=27). Our analysis revealed that a lower expression of DPEP1 and a higher expression of TPX2 in tumors are associated with poor survival in both test and validation cohorts. DPEP1 and TPX2 expressions were independently associated with cancer-specific mortality when adjusted for tumor stage and resection margin status in both univariate and multivariate analyses. In tumor tissues, DPEP1 expression was decreased and TPX2 expression was increased, compared to non-tumor tissues. Furthermore, we demonstrated that mutant KRAS and growth factors such as EGF can decrease DPEP1 and increase TPX2 expression through the MAPK pathway, shedding light on the molecular mechanism of DPEP1 and TPX2 alterations in tumorigenesis and progression. In conclusion, our data provide the first evidence that DPEP1 and TPX2 are prognostic biomarkers, independent of resection margin status and other clinical covariates, in multiple cohorts of PDAC, and may be useful in identifying high-risk patients in order to guide treatment decisions.

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